During the coming year we propose to pursue an examination of the role of the platelet in the pathogenesis of human disease by studies in both experimental animals and in man. Both baboons (Papio cynocephalus) and monkeys (Macaca nemestrina) will be used as experimental animals in carrying out quantitative measurements of endothelial cell loss and proliferation, platelet accumulation and turnover, and measurement of intimal lesion formation in the following experimental settings: 1) hypoxia, 2) antiendothelial cell antibody infusion, and oral sulfinpyrazone administration throughout, 3) three months of sustained homocystinemia, and 4) six months of hyperlipidemia. The relative thrombogenicity of selected prosthetic materials and fabrications will also be determined using the ex vivo baboon A-V shunt. Platelet involvement in human disease will be explored by simultaneously measuring 51Cr-platelet survival, 14C-serotonin platelet survival, and platelet factor IV in selected patients representing a spectrum of vascular disease including: 1) hyperlipidemia; 2) coronary artery disease with a history of successful cardiopulmonary resuscitation; 3) renal vascular disease; 4) diabetes mellitus; 5) scleroderma; and 6) malignancy.